1. Field of the Invention
This invention relates to novel antibacterial agents, the intermediates leading thereto and processes for the preparation of said intermediates. In particular, the invention concerns 4"-deoxy-4"-amino-erythromycin A antibacterial agents, 4"-deoxy-4"-oxo-erythromycin A derivatives as useful intermediates leading to the 4"-amino compounds and processes for the preparation of the 4"-deoxy-4"-oxo-erythromycin A intermediates.
2. Description of the Prior Art
Erythromycin is an antibiotic formed during the culturing of a strain of Streptomyces erythreus in a suitable medium as taught in U.S. Pat. No. 2,653,899. Erythromycin, which is produced in two forms, A and B, is represented by the following structure:
______________________________________ ##STR1## Erythromycin R ______________________________________ A OH B H ______________________________________
The structure reveals that the antibiotic is comprised of three main portions: a sugar fragment known as cladinose, a second sugar moiety containing a basic amino substituent known as desosamine and a fourteen membered lactone ring referred to as erythronolide A or B or, as herein described, the macrolide ring. While the numbering system of the macrolide ring is in unprimed numbers, that of the desosamine is in primed numbers and that of cladinose in double-primed numbers.
Numerous derivatives of erythromycin have been prepared in an effort to modify its biological or pharmacodynamic properties.
U.S. Pat. No. 3,417,077 describes the reaction product of erythromycin and ethylene carbonate as a very active antibacterial agent. U.S. Pat. No. 3,884,903 discloses 4"-deoxy-4"-oxo-erythromycin A and B derivatives as being useful as antibiotics.
Erythromycylamine, the 9-amino derivative of erythromycin A, has been the subject of considerable investigation [British Pat. No. 1,100,504, Tetrahedron Letters, 1645 (1967) and Croatica Chemica Acta, 39, 273 (1967)] and some controversy as to its structural identity [Tetrahedron Letters, 157 (1970) and British Pat. No. 1,341,022]. Sulfonamide derivatives of erythromycylamine are reported in U.S. Pat. No. 3,983,103 to be useful as antibacterial agents. Other derivatives are also reported [Ryden, et al., J. Med. Chem., 16, 1059 (1973) and Massey, et al., J. Med. Chem., 17, 105 (1974)] to have in vitro and in vivo antibacterial activity.